Avicenna Journal of Clinical Medicine

Volume 33, Issue 2

Original Article

Investigating the Temporal Trend and Geographical Distribution of Gallbladder Cancer Burden in Iran between 1990 and 2023: A Study Based on Global Burden of Disease Data

Maryam Hasanzarrini1, Fatemeh Shahbazi2, Amir Mohammad Salehi3*

  1. Clinical Research Development Unit of Shahid Beheshti Hospital, Hamadan University of Medical Sciences, Hamadan, Iran
  2. Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
  3. Fetal and Pediatric Cardiovascular Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran

BRIEF TEXT

Background and Objective

Gallbladder cancer (GBC) is a rare but highly fatal biliary tract malignancy characterized by late diagnosis, aggressive behavior, and poor prognosis. Many studies report five-year survival below 10%, and established risk factors include older age, female sex, gallstones, chronic gallbladder inflammation, gallbladder polyps, biliary abnormalities, obesity, diabetes, smoking, and environmental exposures [1-4]. The burden of GBC is geographically heterogeneous, with marked differences in incidence and mortality across regions, potentially reflecting variation in risk-factor prevalence, genetic background, lifestyle, socioeconomic conditions, access to healthcare, and cancer-registration quality [5, 6]. Because mortality alone does not capture the full population burden, disability-adjusted life years (DALYs), incorporating years of life lost and years lived with disability, provide a broader measure of disease impact [7,8]. The Global Burden of Disease (GBD) study integrates multiple epidemiological and health-system data sources and enables standardized temporal and geographic comparisons [9] [10] [11, 13]. However, national evidence describing long-term trends and provincial disparities in GBC burden in Iran remains limited. Therefore, this study assessed temporal trends in age-standardized incidence, mortality, and DALY rates attributable to GBC among Iranian adults aged ≥20 years from 1990 to 2023 and evaluated their geographic distribution across provinces in 2023.

Materials and Methods

This ecological time-trend study used GBC estimates from the 2023 GBD study for the Iranian population aged ≥20 years. Age-standardized incidence, mortality, and DALY rates per 100,000 population were extracted. Because GBC is extremely uncommon below 20 years of age and more than 99% of the burden occurs among adults, the primary analysis was restricted to individuals aged ≥20 years. A sensitivity analysis using all ages was also performed and showed no meaningful difference from the primary analysis. Temporal trends from 1990 to 2023 were evaluated using Joinpoint Regression software version 6.0.1.0. Year was the independent variable, and each age-standardized rate was the outcome. Models incorporated first-order autocorrelation, allowed up to five joinpoints, and estimated annual percent change (APC) and average annual percent change (AAPC). Permutation testing used a fixed seed of 7160, and the final model was selected according to the Bayesian information criterion [13, 14]. Geographic patterns in 2023 were mapped at the provincial level using ArcGIS 10.8. Age-standardized rates were classified into five quantiles to display spatial heterogeneity.

Results

Overall, GBC burden showed a declining long-term trend in Iran. Between 1990 and 2023, the age-standardized incidence rate decreased by an average of 1.04% per year, while mortality and DALY rates declined by 1.03% and 1.22% annually, respectively (Table 1; Figures 1–3). The temporal pattern was not linear. For incidence, an early decline was followed by a near-stable/slightly increasing period in 1998–2003, a marked decline in 2003–2006, continued moderate reduction through 2014, a temporary increase during 2014–2019, and renewed decline from 2019 to 2023. The overall annual decline in incidence was greater among women (AAPC −1.00%) than men (AAPC −0.51%). Mortality also decreased overall, with a stronger decline among women (AAPC −1.22%) than men (AAPC −0.83%). DALYs followed a similar pattern, with an overall AAPC of −1.22%, including a temporary increase during 2014–2019 and a marked decline from 2019 to 2023. In 2023, substantial geographic heterogeneity was observed across provinces. Qom, Zanjan, Kurdistan, Lorestan, and East Azerbaijan had the highest incidence, mortality, and DALYs, whereas Fars, Hormozgan, Bushehr, and Gilan had the lowest.

Discussion

The overall decline in GBC incidence is consistent with reports from several countries showing decreasing or stable GBC incidence in recent decades [10, 15]. Potential explanations include reductions in modifiable risk factors, improved management of benign gallbladder disease, increased cholecystectomy for symptomatic gallstones, and removal of premalignant lesions [15]. Advances in imaging may also facilitate earlier detection and management of biliary lesions before malignant transformation [16]. The temporary increase in incidence observed from 2014 to 2019 may partly reflect improved cancer-registry coverage and diagnostic capacity, leading to greater case ascertainment [17]. Conversely, the renewed decline after 2019 should be interpreted cautiously because the COVID-19 pandemic disrupted cancer screening, healthcare attendance, diagnostic services, and cancer registration in many settings [18]. The concurrent reductions in mortality and DALYs may reflect improvements in imaging, hepatobiliary surgery, systemic therapy, and multidisciplinary care [16]. Modern systemic treatment, including gemcitabine–cisplatin with the addition of durvalumab in advanced biliary tract cancer, has improved outcomes in selected patients [19], while specialized high-volume centers and precision oncology may further improve survival [20, 21].

The marked provincial heterogeneity identified in 2023 suggests that the national decline has not been uniform. Differences in gallstone disease, obesity, diabetes, metabolic risk, environmental exposures, socioeconomic conditions, access to specialized services, and cancer-registration quality may contribute to this pattern [3, 22]. Genetic and ethnic diversity may also play a role, although the ecological design prevents separation of genetic, environmental, and healthcare-related effects [23-25]. Some observed geographic differences may additionally reflect variation in the completeness and quality of cancer and mortality registration. Thus, GBD estimates should be interpreted as population-level estimates rather than direct measurements of individual-level risk.

Conclusion

From 1990 to 2023, age-standardized incidence, mortality, and DALY rates attributable to GBC among Iranian adults aged ≥20 years generally declined, with more pronounced reductions among women. Nevertheless, important temporal fluctuations and substantial provincial disparities persisted. High-burden provinces, particularly in western and northwestern Iran, may benefit from targeted prevention, earlier diagnosis, improved access to specialized hepatobiliary care, and strengthened cancer-registration systems. Future individual-level analytical studies are needed to clarify the determinants of geographic heterogeneity and to distinguish the contributions of environmental, genetic, socioeconomic, and healthcare-related factors. These findings can support evidence-based cancer-control planning and more efficient allocation of health resources in Iran.

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Table 1. Temporal Trends in Age-Standardized Incidence, Mortality, and DALY Rates Attributable to Gallbladder Cancer among Iranian Adults Aged ≥20 Years, 1990–2023

SexMeasurePeriodAPC (%)AAPC (%)
Both sexesIncidence1990–1998−1.04−1.04
1998–2003+0.05−1.04
2003–2006−2.87−1.04
2006–2014−0.64−1.04
2014–2019+1.47−1.04
2019–2023−1.88−1.04
Mortality1990–1998−1.16−1.03
1998–2003−0.18−1.03
2003–2006−2.79−1.03
2006–2015−0.83−1.03
2015–2019+0.77−1.03
2019–2023−2.70−1.03
DALY1990–1999−1.25−1.22
1999–2003−0.16−1.22
2003–2006−3.19−1.22
2006–2014−1.08−1.22
2014–2019+0.40−1.22
2019–2023−3.04−1.22
WomenIncidence1990–1998−1.01−1.00
1998–2003+0.27−1.00
2003–2006−3.94−1.00
2006–2014−0.97−1.00
2014–2019+1.15−1.00
2019–2023−2.86−1.00
Mortality1990–1998−1.14−1.22
1998–2003+0.12−1.22
2003–2006−3.74−1.22
2006–2014−1.13−1.22
2014–2019+0.34−1.22
2019–2023−3.44−1.22
DALY1990–1998−1.23−1.35
1998–2003−0.04−1.35
2003–2006−4.15−1.35
2006–2014−1.36−1.35
2014–2019+0.17−1.35
2019–2023−3.95−1.35
MenIncidence1990–2014−0.75−0.51
2014–2019+1.86−0.51
2019–2023−1.67−0.51
Mortality1990–2013−1.00−0.83
2013–2020+0.40−0.83
2020–2023−2.58−0.83
DALY1990–2014−1.17−0.99
2014–2019+0.85−0.99
2019–2023−2.17−0.99

Abbreviations: APC, annual percent change; AAPC, average annual percent change; DALY, disability-adjusted life year.

Values and reference numbering correspond to the main manuscript.

Figure 1. Temporal Trend in the Age-Standardized Incidence Rate of Gallbladder Cancer among Iranian Adults, 1990–2023, by Sex

Figure 2. Temporal Trend in the Age-Standardized Mortality Rate of Gallbladder Cancer among Iranian Adults, 1990–2023, by Sex

Figure 3. Temporal Trend in the Age-Standardized Disability-Adjusted Life Year (DALY) Rate Attributable to Gallbladder Cancer among Iranian Adults, 1990–2023, by Sex

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